How specificity is maintained when distinct eukaryotic signal transduction systems share components is a central issue in cell biology that is highly relevant to human cancer. Our long-term objective is a detailed molecular understanding of this ubiquitous phenomenon. To address this question, we have exploited the powerful model system of the budding yeast S. cerevisiae. In this organism, eight proteins are shared between two MAP kinase cascades that signal two distinct developmental programs: 1) the mating pheromone response, and 2) the switch of filamentous growth. Pheromone signaling activates the mating pathway MAPK Fus3. However, due to the sharing of upstream kinases, a fraction of the filamentation pathway MAPK Kss2 is also activated. Our work has revealed that the effects of cross-talk are suppressed because Fus3 induces the phosphorylation and destruction of Tec1, the transcription factor that is activated inducing filamentation-specific transcription via Tec1. To further our understanding of signaling specificity, we will identify the determinants of Tec1 degradation kinetics during mating differentiation, test the hypothesis that there are rapid mechanisms by which Tec1 is inactivated prior to its bulk degradation, and determine how Tec1 is inactivated by the Hog1 MAPK to prevent cross-talk during salt-induced activation of the HOG pathway. Although signaling mechanisms are involved in numerous pathological processes, our studies relate in a particularly important way to human cancer. Tumor proliferation is caused in part by the inappropriate activation of growth-promoting signaling pathways, particularly the Erk MAP kinase pathway, because ras activity induces senescence in precancerous lesions but proliferation in frank malignancies, yet at understanding the principles that determine the specificity of MAP kinase signaling and therefore speak to this central question in oncogenesis.